Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid

<p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn, resulting in hypotonia and muscle weakness. The disease is caused by deletion or mutation in the telomeric copy of <it>SMN </it>gene (<it>SMN1</it>) and clinical severity is in part determined by the copy number of the centromeric copy of the <it>SMN </it>gene (<it>SMN2</it>). The <it>SMN2 </it>mRNA lacks exon 7, resulting in a production of lower amounts of the full-length SMN protein. Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of <it>SMN2 </it>gene. One of these drugs is the valproic acid (VPA), a histone deacetylase inhibitor.</p> <p>Methods</p> <p>Twenty-two patients with type II and III SMA, aged between 2 and 18 years, were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test (Medical Research Council scale-MRC), the Hammersmith Functional Motor Scale (HFMS), and the Barthel Index.</p> <p>Results</p> <p>After 12 months of therapy, the patients did not gain muscle strength. The group of children with SMA type II presented a significant gain in HFMS scores during the treatment. This improvement was not observed in the group of type III patients. The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result. There was an improvement of the daily activities at the end of the VPA treatment period.</p> <p>Conclusion</p> <p>Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01033331">NCT01033331</a></p

Avaliação do tempo de reação em crianças portadoras do transtorno do déficit de atenção/hiperatividade (TDAH)

Attention deficit, impulsivity and hyperactivity are the cardinal features of attention deficit hyperactivity disorder (ADHD) but executive function (EF) disorders, as problems with inhibitory control, working memory and reaction time, besides others EFs, may underlie many of the disturbs associated with the disorder. OBJECTIVE: To examine the reaction time in a computerized test in children with ADHD and normal controls. METHOD: Twenty-three boys (aged 9 to 12) with ADHD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, 2000 (DSM-IV) criteria clinical, without comorbidities, Intelligence Quotient (IQ) >89, never treated with stimulant and fifteen normal controls, age matched were investigated during performance on a voluntary attention psychophysical test. RESULTS: Children with ADHD showed reaction time higher than normal controls. CONCLUSION: A slower reaction time occurred in our patients with ADHD. This findings may be related to problems with the attentional system, that could not maintain an adequate capacity of perceptual input processes and/or in motor output processes, to respond consistently during continuous or repetitive activity.Déficit de atenção, impulsividade e hiperatividade são os pontos cardinais do transtorno do déficit de atenção/hiperatividade (TDAH), mas as desordens da função executiva (FE) tais como os problemas no controle inibitório, memória operacional e tempo de reação, dentre outras funções executivas (FEs) podem estar subjacentes a muitos distúrbios associados a esta desordem. OBJETIVO: Avaliar o tempo de reação em meninos portadores do TDAH. MÉTODO: Participaram 23 pacientes do sexo masculino, de idade entre 9 a 12 anos de idade, com diagnóstico de TDAH sem co-morbidades, estabelecido segundo os critérios do Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV), com Quoeficiente Intelectual (QI) >89, que não tivessem sido medicados para o TDAH. Grupo controle, seguindo os mesmos critérios em relação ao sexo, idade, QI. O teste utilizado foi o teste psicofísico da atenção voluntária (TPAV). RESULTADOS: Os pacientes do TDAH apresentaram maior tempo de reação na execução do teste em relação aos controles. CONCLUSÃO: O tempo de reação apresentou-se mais lento em nossos pacientes portadores de TDAH. Estes achados podem estar relacionados aos problemas do sistema atencional; este grupo não pôde manter uma adequada capacidade de percepção de dados processados e/ou, em responder regularmente durante atividades contínuas ou repetitivas

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation